Statin induced myopathy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby

Overview

Definition

Statin induced myopathy is a spectrum of muscular problems caused by the intake of statin. Myopathy by definition is the abnormal function of the muscle. The spectrum of statin induced myopathy includes:

Myalgia

  • Myalgia is defined as one or combination of muscle weakness, tenderness or pain.
  • Patients usually complain of cramping feeling in the muscles.
  • Creatine kinase may be normal or minimally elevated.

Asymptomatic increase in creatine kinase

Myositis

  • Myositis is the inflammation of the muscle characterised by muscular complaints in the setting of elevated creatine kinase up to ten folds.

Rhabdomyositis

  • Rhabdomyositis is the acute degeneration of the skeletal muscle.
  • It is a potentially lethal condition due to its associated nephrotoxicity caused by myoglobinuria and myoglobinemia.
  • Creatine kinase is elevated in rhabdomyosistis similarly to myositis.
  • The complications of rhabdomyositis are acute tubular necrosis, hypocalcemia, hyperkalemia, metabolic acidosis, hyperuricemia, DIC and cardiomyopathy.[1]

Other Statin Induced Myopathies

  • Elevated creatine kinase after statin withdrawal[2]
  • Autoimmune myopathy requiring immunosuppressive therapy[3]

Prevalence

Risk Factors

Pathophysiology

Statin induced myopathies has a complex poorly understood multifactorial pathophysiology. It is postulated that statin causes myopathy through the following changes:

  • Changes in cholesterol content and alteration of the membrane fluidity of skeletal muscle cells which disrupts their normal function
  • Changes in skeletal muscle cells membrane electrical properties
  • Changes in Na+/K+ pump density resulting in decreased production of ATP
  • Changes in the excitation-contraction coupling
  • Changes in the cell surface receptor transduction cascades
  • Decreased synthesis of ubiquinone (Q10), a component of the mitochondrial electron transport chain, leading to decreased ATP production and decreased free radical scavenging
  • Increased intracellular calcium causing apoptosis of the skeletal muscle cells
  • Decreased mevalonate metabolism products, particularly isoprenoids, leading to a chain of events that culminate in apoptosis of skeletal muscle cells[4]

Treatment

References

  1. Baker, S.K. & Tarnopolsky, M.A. (2001). Statin myopathies: pathophysiologic and clinical perspectives. Clin. Invest. Med., 24(5): 258-272.
  2. Thompson PD, Clarkson P, Karas RH (2003). "Statin-associated myopathy". JAMA. 289 (13): 1681–90. doi:10.1001/jama.289.13.1681. PMID 12672737.
  3. Radcliffe KA, Campbell WW (2008). "Statin myopathy". Curr Neurol Neurosci Rep. 8 (1): 66–72. PMID 18367041.
  4. Dirks AJ, Jones KM (2006). "Statin-induced apoptosis and skeletal myopathy". Am J Physiol Cell Physiol. 291 (6): C1208–12. doi:10.1152/ajpcell.00226.2006. PMID 16885396.